Failure of ciliary function and concomitant mucus stagnation result in respiratory impairment, one of the prime factors in death from cystic fibrosis. The purpose of this study is to clearly resolve the question of whether cystic fibrosis serum and serum from individuals heterozygous for the disease contain a factor(s) which induces ciliary dyskinesia in tracheal eipthelium to account for respiratory impairment. The primary objectives of this research will be: a) to determine whether or not cystic fibrosis and heterozygote sera and purified serum factor(s) induce ciliary dyskinesia as a primary effect or whether this event is a secondary effect of cytolysis, b) to purify and characterize the factor and compare its action on ciliary function and cell structure with the effects of unpurified sera, and c) establish whether the sera and serum factor(s) have a comparable effect on human respiratory epithelium to account for respiratory impairment. Tissue from tracheas of rabbits will be removed and placed in both organ and cell culture. Both the ciliated epithelium and ciliated cells in culture will be exposed to cystic fibrosis serum, serum from heterozygotes, presumed normal serum and purified serum factor. The epithelium will be evaluated for change in either rate or organization of ciliary beat utilizing a photomultiplier system and Fast Fourier transform system developed in our laboratory. Tissue so evaluated will be examined with both scanning and transmission electron microscopy for evidence of increased goblet cell secretion, changes in ciliary structure and cytolysis. Serum factor effects on epithelium cultured to produce a condition of high and low mucus content will also be investigated. Parallel comparisons will be made utilizing human tracheal epithelium from surgical resection. The purified serum factor will be characterized as to molecular weight, carbohydrate content and possible structure, amino acid composition, peptide mapping and amino acid sequence. With these techniques we can correlate quantitatively effects of known amounts of purified CF factor(s) with ciliary dyskinesia and determine its impact on human tracheal epithelium. This information should give good indication of possible roles of CF factor(s) in the respiratory impairment associated with cystic fibrosis.